Cardiac Connexin-43 Hemichannels and Pannexin1 Channels: Provocative Antiarrhythmic Targets

International Journal of Molecular Sciences

Barbara Szeiffova Bacova¹  Katarina Andelova¹  Matus Sykora¹  Narcis Tribulova¹  Tamara Egan Benova¹  Peter Hlivak²  EmilianoRaul Diez³  NataliaJorgelina Prado³ 

[1] Centre of Experimental Medicine, Slovak Academy of Sciences, Institute for Heart Research, 84104 Bratislava, Slovakia;Department of Arrhythmias and Pacing, National Institute of Cardiovascular Diseases, Pod Krásnou Hôrkou 1, 83348 Bratislava, Slovakia;Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas, M5500 Mendoza, Argentina;

关键词: cardiac arrhythmias;    Cx43 hemi-channels;    pannexin1 channels;    mimetic peptides;    cardio-protection;   

DOI  :  10.3390/ijms22010260

来源: DOAJ

【 摘 要 】

Cardiac connexin-43 (Cx43) creates gap junction channels (GJCs) at intercellular contacts and hemi-channels (HCs) at the peri-junctional plasma membrane and sarcolemmal caveolae/rafts compartments. GJCs are fundamental for the direct cardiac cell-to-cell transmission of electrical and molecular signals which ensures synchronous myocardial contraction. The HCs and structurally similar pannexin1 (Panx1) channels are active in stressful conditions. These channels are essential for paracrine and autocrine communication through the release of ions and signaling molecules to the extracellular environment, or for uptake from it. The HCs and Panx1 channel-opening profoundly affects intracellular ionic homeostasis and redox status and facilitates via purinergic signaling pro-inflammatory and pro-fibrotic processes. These conditions promote cardiac arrhythmogenesis due to the impairment of the GJCs and selective ion channel function. Crosstalk between GJCs and HCs/Panx1 channels could be crucial in the development of arrhythmogenic substrates, including fibrosis. Despite the knowledge gap in the regulation of these channels, current evidence indicates that HCs and Panx1 channel activation can enhance the risk of cardiac arrhythmias. It is extremely challenging to target HCs and Panx1 channels by inhibitory agents to hamper development of cardiac rhythm disorders. Progress in this field may contribute to novel therapeutic approaches for patients prone to develop atrial or ventricular fibrillation.

【 授权许可】

Unknown